scholarly journals A one-protein signaling pathway in the innate immune system

2016 ◽  
Vol 1 (2) ◽  
pp. eaah6184-eaah6184
Author(s):  
Megan H. Orzalli ◽  
Jonathan C. Kagan
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Innate Immune System ◽  
Innate Immune ◽  
Protein Signaling

scholarly journals THU0010 GENES ASSOCIATED WITH NUCLEOTIDE OLIGOMERIZATION DOMAIN-LIKE RECEPTOR SIGNALING PATHWAY ARE UPREGULATED IN CUTANEOUS LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 217.3-217
Author(s):  
I. Calderon ◽  
R. Mina
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Innate Immune System ◽  
Cutaneous Lupus Erythematosus ◽  
Skin Lesions ◽  
Innate Immune ◽  
Normal Controls ◽  
Cutaneous Lupus ◽  
Skin Samples

Background:Cutaneous Lupus Erythematosus (CLE) is a disfiguring autoimmune skin disorder with several subtypes: discoid lupus, subacute cutaneous lupus, and acute cutaneous lupus. CLE is associated with defects in the adaptive immune system, and, at times, systemic involvement. The innate immune system is likely involved as seen in the presence of interface dermatitis, which is observed in viral exanthems, and improvement of CLE using inhibitors to membrane-bound Pattern Recognition Receptors.Objectives:Compare the expression of genes associated with the innate immune system in active CLE skin lesions of different subtypes compared to normal skin controls.Methods:Five datasets selected from the Gene Expression Omnibus (GEO) were analyzed using GEO2R to compare the gene expressions between different subtypes of CLE. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, Gene Card, and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis were used to identify the interaction and function of specific genes.Results:There were a total of 147 CLE skin samples and 52 normal controls. Genes associated with the Nucleotide-Binding Oligomerization Domain-Like Receptor (NLR) signaling pathway were upregulated in CLE skin samples (adjusted p-value < 0.001). Five genes associated with the NLR signaling pathway, STAT1, OAS1, OAS2, OAS3, and AIM2, were found to be upregulated in skin samples of CLE patients in all datasets, regardless of type, compared to normal controls in all datasets. These five genes are associated with transcription activation, regulation of viral infection, and interferon response.Conclusion:Genes associated with the NLR signaling pathway are upregulated in the skin lesions of CLE patients compared to normal controls, supporting the role of the innate immune system in CLE. Further validation studies using experimental methods are needed.References:[1]Enhanced inflammasome activity in systemic lupus erythematosus is mediated via type I interferon upregulation of interferon regulatory factor 1. Liu J, et al. Arth Rheum. 2017; 69(9): 1840-1849.Disclosure of Interests:None declared

scholarly journals An analysis of the mechanism of aging: endogenous viral stimulus and the deleterious effect of chronic inflammation

2019 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Innate Immune System ◽  
Mapk Pathway ◽  
Lipid Synthesis ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Ros Production

This article describes a putative mechanism of aging based on the interaction of endogenous viral particles with the receptors of the innate immune system leading to producing pro-inflammatory cytokines. The innate immune response induces a complex of signaling pathways leading to senescence or tumorigenesis. The fate of a cell is depended on the activity of the p53 tumor-suppressive signaling pathway. Chronic inflammation is characterized by upregulation of the NF-kB signaling. The NF-kB protein stimulates the expression of matrix metalloproteinases (MMPs) leading to remodeling of extracellular matrix. The extracellular matrix alterations induce the loss of stem cell environment and their depletion. The innate immune system also mediates the PI3K-Akt-mTOR signaling pathway that inhibits autophagy and transforms energy metabolism providing cell senescence, high level of blood glucose, high lipid synthesis and mitochondrial alterations. The STAT3-HIF1 signaling pathway suppresses oxidative phosphorylation increasing ROS production and promoting the MAPK pathway leading to excessive cell proliferation. The increased ROS production causes the global DNA and histone demethylation contributing to retrotransposon reactivation whose activity leads to genome instability. However, the activity of retrotransposons may be partly explained by their role in adaptation. Among retrotransposons, endogenous retroviruses may be considered as an intrinsic stimulus for the innate immune system and are also able to avoid the adaptive immune system. Therefore, I consider endogenous retroviruses as promising targets in anti-aging therapies

scholarly journals An analysis of the mechanism of aging: endogenous viral stimulus and the deleterious effect of chronic inflammation

2019 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Innate Immune System ◽  
Mapk Pathway ◽  
Lipid Synthesis ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Ros Production

This article describes a putative mechanism of aging based on the interaction of endogenous viral particles with the receptors of the innate immune system leading to producing pro-inflammatory cytokines. The innate immune response induces a complex of signaling pathways leading to senescence or tumorigenesis. The fate of a cell is depended on the activity of the p53 tumor-suppressive signaling pathway. Chronic inflammation is characterized by upregulation of the NF-kB signaling. The NF-kB protein stimulates the expression of matrix metalloproteinases (MMPs) leading to remodeling of extracellular matrix. The extracellular matrix alterations induce the loss of stem cell environment and their depletion. The innate immune system also mediates the PI3K-Akt-mTOR signaling pathway that inhibits autophagy and transforms energy metabolism providing cell senescence, high level of blood glucose, high lipid synthesis and mitochondrial alterations. The STAT3-HIF1 signaling pathway suppresses oxidative phosphorylation increasing ROS production and promoting the MAPK pathway leading to excessive cell proliferation. The increased ROS production causes the global DNA and histone demethylation contributing to retrotransposon reactivation whose activity leads to genome instability. However, the activity of retrotransposons may be partly explained by their role in adaptation. Among retrotransposons, endogenous retroviruses may be considered as an intrinsic stimulus for the innate immune system and are also able to avoid the adaptive immune system. Therefore, I consider endogenous retroviruses as promising targets in anti-aging therapies

L-Threonine upregulates β-defensins expression by activating NF-κB signaling pathway and suppressing SIRT1 expression in porcine intestinal epithelial cells

2021 ◽  
Author(s):  
Chenxi Wang ◽  
Yang Yang ◽  
Nan Gao ◽  
Jing Lan ◽  
Xiujing Dou ◽  
...  
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Antimicrobial Peptide ◽  
Signaling Pathway ◽  
Innate Immune System ◽  
Intestinal Epithelial Cells ◽  
Innate Immune ◽  
Pivotal Role ◽  
Intestinal Epithelial ◽  
New Strategy

The use of antimicrobial peptide (AMP), found in all forms of life and playing a pivotal role in the innate immune system, has been developed as a new strategy for...

scholarly journals Activation of the RLR/MAVS Signaling Pathway by the L Protein of Mopeia Virus

2016 ◽  
Vol 90 (22) ◽  
pp. 10259-10270 ◽  
Author(s):  
Lei-Ke Zhang ◽  
Qi-Lin Xin ◽  
Sheng-Lin Zhu ◽  
Wei-Wei Wan ◽  
Wei Wang ◽  
...  
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Innate Immune System ◽  
Hemorrhagic Fever ◽  
Polymerase Activity ◽  
Innate Immune ◽  
Type I ◽  
Human Pathogens ◽  
Content Type ◽  
Viral Components

ABSTRACT The family Arenaviridae includes several important human pathogens that can cause severe hemorrhagic fever and greatly threaten public health. As a major component of the innate immune system, the RLR/MAVS signaling pathway is involved in recognizing viral components and initiating antiviral activity. It has been reported that arenavirus infection can suppress the innate immune response, and NP and Z proteins of pathogenic arenaviruses can disrupt RLR/MAVS signaling, thus inhibiting production of type I interferon (IFN-I). However, recent studies have shown elevated IFN-I levels in certain arenavirus-infected cells. The mechanism by which arenavirus infection induces IFN-I responses remains unclear. In this study, we determined that the L polymerase (Lp) of Mopeia virus (MOPV), an Old World (OW) arenavirus, can activate the RLR/MAVS pathway and thus induce the production of IFN-I. This activation is associated with the RNA-dependent RNA polymerase activity of Lp. This study provides a foundation for further studies of interactions between arenaviruses and the innate immune system and for the elucidation of arenavirus pathogenesis. IMPORTANCE Distinct innate immune responses are observed when hosts are infected with different arenaviruses. It has been widely accepted that NP and certain Z proteins of arenaviruses inhibit the RLR/MAVS signaling pathway. The viral components responsible for the activation of the RLR/MAVS signaling pathway remain to be determined. In the current study, we demonstrate for the first time that the Lp of MOPV, an OW arenavirus, can activate the RLR/MAVS signaling pathway and thus induce the production of IFN-I. Based on our results, we proposed that dynamic interactions exist among Lp-produced RNA, NP, and the RLR/MAVS signaling pathway, and the outcome of these interactions may determine the final IFN-I response pattern: elevated or reduced. Our study provides a possible explanation for how IFN-I can become activated during arenavirus infection and may help us gain insights into the interactions that form between different arenavirus components and the innate immune system.

scholarly journals An analysis of the mechanism of aging: endogenous viral stimulus and the deleterious effect of chronic inflammation

2018 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Innate Immune System ◽  
Mapk Pathway ◽  
Lipid Synthesis ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Ros Production

This article describes a putative mechanism of aging based on the interaction of endogenous viral particles with the receptors of the innate immune system leading to producing pro-inflammatory cytokines. The innate immune response induces a complex of signaling pathways leading to senescence or tumorigenesis. The fate of a cell is depended on the activity of the p53 tumor-suppressive signaling pathway. Chronic inflammation is characterized by upregulation of the NF-kB signaling. The NF-kB protein stimulates the expression of matrix metalloproteinases (MMPs) leading to remodeling of extracellular matrix. The extracellular matrix alterations induce the loss of stem cell environment and their depletion. The innate immune system also mediates the PI3K-Akt-mTOR signaling pathway that inhibits autophagy and transforms energy metabolism providing cell senescence, high level of blood glucose, high lipid synthesis and mitochondrial alterations. The STAT3-HIF1 signaling pathway suppresses oxidative phosphorylation increasing ROS production and promoting the MAPK pathway leading to excessive cell proliferation. The increased ROS production causes the global DNA and histone demethylation contributing to retrotransposon reactivation whose activity leads to genome instability. However, the activity of retrotransposons may be partly explained by their role in adaptation. Among retrotransposons, endogenous retroviruses may be considered as an intrinsic stimulus for the innate immune system and are also able to avoid the adaptive immune system. Therefore, I consider endogenous retroviruses as promising targets in anti-aging therapies

scholarly journals An analysis of the mechanism of aging: endogenous viral stimulus and the deleterious effect of chronic inflammation

2019 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Innate Immune System ◽  
Mapk Pathway ◽  
Lipid Synthesis ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Ros Production

This article describes a putative mechanism of aging based on the interaction of endogenous viral particles with the receptors of the innate immune system leading to producing pro-inflammatory cytokines. The innate immune response induces a complex of signaling pathways leading to senescence or tumorigenesis. The fate of a cell is depended on the activity of the p53 tumor-suppressive signaling pathway. Chronic inflammation is characterized by upregulation of the NF-kB signaling. The NF-kB protein stimulates the expression of matrix metalloproteinases (MMPs) leading to remodeling of extracellular matrix. The extracellular matrix alterations induce the loss of stem cell environment and their depletion. The innate immune system also mediates the PI3K-Akt-mTOR signaling pathway that inhibits autophagy and transforms energy metabolism providing cell senescence, high level of blood glucose, high lipid synthesis and mitochondrial alterations. The STAT3-HIF1 signaling pathway suppresses oxidative phosphorylation increasing ROS production and promoting the MAPK pathway leading to excessive cell proliferation. The increased ROS production causes the global DNA and histone demethylation contributing to retrotransposon reactivation whose activity leads to genome instability. However, the activity of retrotransposons may be partly explained by their role in adaptation. Among retrotransposons, endogenous retroviruses may be considered as an intrinsic stimulus for the innate immune system and are also able to avoid the adaptive immune system. Therefore, I consider endogenous retroviruses as promising targets in anti-aging therapies

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